E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders (NMO/NMOSD) |
Neuromielitis óptica y trastornos del espectro de la neuromielitis óptica (NMO/TENMO) |
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E.1.1.1 | Medical condition in easily understood language |
Neuromyelitis optica (NMO) and NMO Spectrum Disorders, involve inflammation and damage of the optic nerve (optic neuritis), spinal cord (myelitis) and certain areas of the brain. |
La neuromielitis óptica y los trastornos del espectro de la neuromielitis óptica incluyen inflamación y daño del nervio óptico (neuritis óptica), médula espinal (mielitis) y ciertas áreas del cerebro. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029322 |
E.1.2 | Term | Neuromyelitis optica |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of MEDI-551 versus placebo in reducing the risk of an NMO/NMOSD attack |
Comparar la eficacia de MEDI-551 respecto a placebo para reducir el riesgo de una crisis de NMO/TENMO |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the long-term efficacy of MEDI-551 by means of annualized attack rate. 2. To evaluate the safety and tolerability of MEDI-551 3. To characterize the pharmacokinetic (PK) profile and immunogenicity of MEDI-551 |
1. Determinar la eficacia a largo plazo de MEDI-551 mediante la tasa anualizada de crisis. 2. Evaluar la seguridad y tolerabilidad de MEDI-551 3. Definir el perfil farmacocinético (FC) y la inmunogenicidad de MEDI-551 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Men and women 18 years or older with diagnosis of NMO/NMOSD. 2) Confirmation of NMO/NMOSD status: a.) AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years. b.) AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years. 3) Able and willing to give written informed consent and comply with the requirements of the study protocol. 4) EDSS <= 7.5 (8 in special circumstances). 5) Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product. |
1) Hombres y mujeres de 18 años de edad o más con diagnóstico de NMO/TENMO. 2) Confirmación del estado de NMO/TENMO: a.) NMO/TENMO con AQP4 IgG positivo en suero con al menos una crisis con necesidad de tratamiento de rescate en el último año o dos crisis con necesidad de tratamiento de rescate en los últimos 2 años. b.) NMO con AQP4 IgG negativo en suero con al menos una crisis con necesidad de tratamiento de rescate en el último año o dos crisis con necesidad de tratamiento de rescate en los últimos 2 años. 3) Capaz y dispuesto a dar su consentimiento informado por escrito y cumplir con los requisitos del protocolo de estudio 4) EDSS <= 7,5 (8 en circunstancias especiales). 5) Los hombres y mujeres con posibilidad reproductiva deben estar de acuerdo en utilizar un método anticonceptivo sumamente eficaz desde la selección hasta 6 meses después de la última dosis del producto en investigación. |
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E.4 | Principal exclusion criteria |
1) Lactating and pregnant females. 2) Treatment with any investigational agent within 4 weeks of screening. 3) Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy. 4) Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization. 5) History of of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization. 6) Receipt of the following at any time prior to randomization: a) Alemtuzumab b) Total lymphoid irradiation c) Bone marrow transplant d) T-cell vaccination therapy 7) Receipt of rituximab or any experimental B-cell depleting agent, unless the subject´s B cells have returned to lower limit of normal (LLN) or greater prior to randomization. 8) Receipt of IVIG within 1 month prior to randomization. 9) Receipt of any of the following within 3 months prior to randomization: a) Natalizumab (Tysabri®) b) Cyclosporin c) Methotrexate d) Mitoxantrone e) Cyclophosphamide f) Tocilizumab g) Eculizumab 10) History of Hepatitis B and/or Hepatitis C (Hep B/C at screening). 11) Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection. 12) History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to randomization. |
1) Mujeres embarazadas o lactantes. 2) Tratamiento con un producto en investigación en las 4 semanas tras la selección. 3) Antecedentes conocidos de alergia o reacción grave a alguno de los componentes de la formulación del producto en investigación o antecedentes de anafilaxia tras recibir cualquier tratamiento biológico 4) Infección viral o bacteriana conocida activa grave o cualquier otro episodio de infección que precise hospitalización. 5) Datos de abuso de alcohol, drogas o sustancias químicas o antecedentes recientes de tal abuso menos de un año antes de la aleatorización. 6) Recepción de los siguientes tratamientos en cualquier momento antes de la aleatorización: a. Alemtuzumab. b. Irradiación linfática total. c. Trasplante de médula ósea. d. Vacuna de linfocitos T. 7) Recepción de rituximab o cualquier fármaco destructor de linfocitos B experimental, a menos que el recuento de linfocitos B del sujeto haya vuelto al límite inferior de la normalidad (LIN) o una cifra superior antes de la aleatorización. 8) Recepción de IGIV en el mes previo a la aleatorización 9) Recepción de alguno de los medicamentos siguientes en los 3 meses previos a la aleatorización: a. Natalizumab (Tysabri®) b. Ciclosporina. c. Metotrexato. d. Mitoxantrona. e. Ciclofosfamida. f. Tocilizumab. g. Eculizumab. 10) Antecedentes de hepatitis B y/o hepatitis C (hepatitis B/C en el momento de selección) 11) Antecedentes conocidos de inmunodeficiencia primaria (congénita o adquirida) o de una enfermedad subyacente, como infección por el virus de la inmunodeficiencia humana (VIH). 12) Antecedentes de cáncer, aparte de un carcinoma espinocelular o basocelular de piel tratado, con éxito demostrado del tratamiento curativo más de 3 meses antes de la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to an NMO/NMOSD attack determined by Adjudication Committee. |
Tiempo hasta una crisis de NMO/TENMO determinado por el comité de adjudicación. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
on or before Day 197 |
durante o antes del dia 197 |
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E.5.2 | Secondary end point(s) |
1) Attack Rate 2) Number of subjects with Adverse Events 3) PK profile 4) Incidence of anti-drug antibodies (ADAs) directed against MEDI-551 |
1) Tasa de crisis 2) Número de sujetos con acontecimientos adversos 3) Perfil farmacocinético 4) Incidencia de anticuerpos contra el fármaco (ACF) dirigidos contra MEDI-551 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of Randomized-controlled Period and End of Study |
Fin del período controlado aleatorizado y final del estudio |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Período de extensión abierto |
Open label extension |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Colombia |
Czech Republic |
Estonia |
Germany |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Mexico |
Moldova, Republic of |
New Zealand |
Peru |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This will occur when the last subject completes the 52-week safety follow up. |
El final del estudio se define como la fecha de la última visita/evaluación especificada en el protocolo (incluido el contacto telefónico) del último sujeto del estudio. Tendrá lugar cuando el último sujeto complete el período de seguimiento de la seguridad de 52 semanas. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |